ObjectiveTo screen out the transcriptomes related to the intervention of Wuzi Yanzongwan on the spermatogenic function of semi-castrated male mice， and to explore its potential mechanism in the intervention of the progress of low spermatogenic function. MethodBalb/c mice were randomly divided into sham-operated group， model group， testosterone propionate group（0.2 mg·kg^-1·d^-1， intramuscular injection） and Wuzi Yanzongwan group（1.56 g·kg^-1·d^-1， intragastric administration） according to body weight， with 12 mice in each group. The right testicle and epididymis were extracted from the model group and the drug administration group to construct the semi-castrated model of low spermatogenic function， while the fur and the right scrotum of the sham-operated group were only cut and immediately sterilized and sutured. At the end of the intervention， hematoxylin-eosin（HE） staining was used to observe the histopathology of testis， enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of serum testosterone（T）， luteinizing hormone（LH） and follicle stimulating hormone（FSH）. The sperm count and motility of epididymis were measured by automatic sperm detector of small animal. Transcriptomic microarray technology was used to detect the mRNA expression level of testicular tissue in each group， the transcriptome of genes related to the regulation of Wuzi Yanzongwan was screened， and three mRNAs were selected for Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） to verify the transcriptome data. Through the annotation analysis of Gene Ontology（GO） and the signaling pathway analysis of Kyoto Encyclopedia of Genes and Genomes（KEGG）， the related functions of drugs regulating transcriptome were analyzed. ResultCompared with the sham-operated group， the testicular tissue of mice in the model group showed spermatogenic injury， contraction and vacuolization of the seminiferous tubules， reduction of spermatogenic cells at all levels， widening of the interstitial space， obstruction of spermatogonial cell development and other morphological abnormalities， and serum T significantly decreased， LH significantly increased（P<0.01）， and FSH elevated but no statistically significant difference， the count and vitality of epididymal sperm significantly decreased（P<0.01）. There were 882 differentially expressed mRNAs in the testicular tissues， of which 565 were up-regulated and 317 were down-regulated. Cluster analysis showed that these differentially expressed mRNA could effectively distinguish between the sham-operated group and the model group. Compared with the model group， the damage to testicular tissue in the Wuzi Yanzongwan group was reduced， the structure of the seminiferous tubules was intact， vacuolization was reduced， and the number of spermatogenic cells at all levels was significantly increased and arranged tightly. The serum T significantly increased， LH significantly decreased（P<0.01）， and FSH decreased but the difference was not statistically significant. The count and vitality of sperm in the epididymis were significantly increased（P<0.01）. Moreover， Wuzi Yanzongwan could regulate 159 mRNA levels in the testes of semi-castrated mice， of which 32 were up-regulated and 127 were down-regulated， and the data of the transcriptome assay was verified to be reliable by Real-time PCR. GO and KEGG analysis showed that the transcriptome functions regulated by Wuzi Yanzongwan were involved in the whole cell cycle process of sperm development such as sex hormone production of interstitial cells in testis， renewal， differentiation， metabolism， apoptosis and signal transduction of spermatogenic cells， and were closely related to the biological behaviors of signaling pathways such as spermatogenic stem cell function， endoplasmic reticulum protein processing and metabolic program. ConclusionWuzi Yanzongwan can effectively improve the low spermatogenic function of semi-castrated male mice， and its mechanism may be related to the regulation of testicular transcriptional regulatory network， the synthesis of sex hormones in testicular interstitial cells， the function of spermatogenic stem cells， the whole cell cycle process of spermatogenesis， as well as the expression of endoplasmic reticulum protein processing and metabolic program related genes transcription.

Animals ; Hepatic Stellate Cells ; Liver Cirrhosis/pathology* ; RNA, Long Noncoding/genetics* ; Rats

DNA, Mitochondrial ; genetics ; Humans ; MELAS Syndrome ; diagnosis ; diagnostic imaging ; genetics ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Mutation ; genetics

PURPOSE: Iron deficiency anemia (IDA) is one of the most common nutritional deficiencies in children on a weaning diet. We investigated weaning practices in infants and children, as well as their mothers' knowledge about weaning. METHODS: We investigated 129 children with IDA and 166 without IDA (aged 6-36 months) who had visited 10 university hospitals between March 2006 and July 2007. We investigated the hematologic values of both groups. A questionnaire on weaning was answered by the mothers of these children. RESULTS: The hematologic values in the IDA group showed a significant difference from those in the comparison group (P<0.05). Children who were solely breastfed until 6 months of age were 85%, 34% (P<0.05), and weaning was started by 6.3, 6.4 months, respectively (P>0.05). Rice gruel, boiled rice, and fruit juice accounted for approximately 8 0% of the starting foods in both groups (P>0.05). Only 40% of the children in the IDA group had a balanced diet within a month, versus 38% in the comparison group. In response to questions about the necessity of iron-fortified foods for breast-fed infants, less than 50% of mothers in both groups answered correctly. In the IDA group, 42% showed serum ferritin less than 10 ng/ mL, while 92% showed serum MCV less than 72 fL. CONCLUSION: In conclusion, collection of information on history should be thorough for feeding and selective examinations for IDA in high-risk groups. Considering the adaptation period, we suggest beginning children on a weaning diet at 45 months. In addition, we need to educate mothers on weaning practice, especially on the necessity of iron-fortified foods for breast-fed infants.
Anemia, Iron-Deficiency ; Child ; Diet ; Ferritins ; Fruit ; Hospitals, University ; Humans ; Infant ; Iron ; Malnutrition ; Mothers ; Surveys and Questionnaires ; Weaning

BACKGROUND: The aim of this study was to investigate the prevalence, clinical and laboratory findings of hereditary hemolytic anemia (HHA) in Korea from 1997 to 2006 and to develop the appropriate diagnostic approach for HHA. METHODS: By the use of questionnaires, information on the clinical and laboratory findings ofHHA diagnosed from 1997 to 2006 in Korea was collected and analyzed retrospectively. A total of 431 cases were enrolled in this study from 46 departments of 35 hospitals. RESULTS: The overall frequency of HHA did not change through the 10-year period for pediatrics but did show an increasing tendency for internal medicine. The overall male to female sex ratio did not show sex predominance (1.17:1), but a significant male predominance with a ratio of 1.49:1 was seen for pediatrics while a significant female predominance with a ratio of 1:1.97 was seen forinternal medicine. Of the total cases, 74.2% (282/431) were diagnosed before the age of 15 years. The etiologies of HHA were classified as red cell membrane defects, hemoglobinopathies, red cell enzyme deficiencies and unknown causes. There were 382 cases (88.6%) of red cell membrane defects with 376 cases (87.2%) of hereditary spherocytosis and 6 cases (1.4%) of hereditary elliptocytosis, 20 cases (4.6%) of hemoglobinopathies with 18 cases (4.2%) of beta-thalassemia, a case (0.2%) of alpha-thalassemia and a case (0.2%) of Hemoglobin Madrid, 7 cases (1.6%) of red cell enzyme deficiencies with 5 cases (1.2%) of glucose-6- phosphate dehydrogenase (G-6-PD) deficiency, a case (0.2%) of pyruvate kinase (PK) deficiency and a case (0.2%) of enolase deficiency, and 22 cases (5.1%) of unknown causes. The most common chief complaint in pediatric patients was pallor and that in adult patients was jaundice. In the red cell membrane defect group of patients, the level of hemoglobin was significantly higher than in adult patients. The mean corpuscular volume, mean corpuscular hemoglobin, corrected reticulocyte count, total and indirect bilirubin level and lactate dehydrogenase levels in the hemoglobinopathy group of patients were significantly lower than the values in the red cell membrane defect group of patients. The mean concentration of G-6-PD was 0.8+/-0.7U/1012RBC in the G-6-PD deficient patients, PK was 1.7U/1010 RBC in the PK deficient patient, and the level of enolase was 0.04U/g of Hb in the enolase deficient patient. CONCLUSION: The most prevalent cause of HHA in Korea during 1997 to 2006 was hereditary spherocytosis, but HHA by other causes such as hemoglobinopathy and red cell enzyme deficiency gradually increased with the development of molecular diagnostic methods and increasing general interest. However, the etiologies of HHA need to be pursued further in 5.1% of the patients. An systematic standard diagnostic approach is needed in a nationwide prospective study for correct diagnoses and appropriate management of HHA.
Adult ; alpha-Thalassemia ; Anemia, Hemolytic, Congenital* ; beta-Thalassemia ; Bilirubin ; Cell Membrane ; Diagnosis ; Elliptocytosis, Hereditary ; Erythrocyte Indices ; Female ; Hemoglobinopathies ; Humans ; Internal Medicine ; Jaundice ; Korea* ; L-Lactate Dehydrogenase ; Male ; Oxidoreductases ; Pallor ; Pathology, Molecular ; Pediatrics ; Phosphopyruvate Hydratase ; Prevalence ; Pyruvate Kinase ; Reticulocyte Count ; Retrospective Studies* ; Sex Ratio ; Surveys and Questionnaires

PURPOSE: Wilms tumor is the most common malignant renal tumor in children. We investigated the epidemiology, clinical features and treatment outcome of the children with Wilms tumor in Korea during the recent 10 years. METHODS: Two hundred forty six patients were enrolled between January 1991 and December 2000 from 26 major hospitals in Korea. The data regarding the clinical features including sex, age, pathologic type, prognostic factor and treatment outcome of patients were analyzed retrospectively by review of patient's medical records. Kaplan-Meier survival curves were constructed, The differences between groups were analyzed by log-rank test. RESULTS: There were 130 males and 116 females. The incidence between the age of 1~4 years was the highest with 66.2%. The annual incidence rate per 1, 000, 000 population varied from 1.9 to 2.1. The 10 years overall survival rate according to sex, clinical stage, pathologic type and relapse were as follows: 88.6% in male, 90.9% in female, 100% in stage I, 94.7% in stage II, 92.1% in stage III, 63.4% in stage IV, 85.7% in stage V, 95.3% in favorable histology, 64.1% in unfavorable histology, 94.8% in non-relapse, and 40.9% in relapse. The relapse rate was 12%. The 10 years overall survival rate of 246 patients were 89.1%. CONCLUSION: Our results could provide the most recent and important clinical information on Wilms tumor of children in Korea.
Child ; Epidemiology* ; Female ; Humans ; Incidence ; Kaplan-Meier Estimate ; Korea* ; Male ; Medical Records ; Recurrence ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; Wilms Tumor*

PURPOSE: Malignant lymphoma is the primary malignant tumor derived from lymphoid organs. It is composed of Hodgkin's disease and non-Hodgkin lymphoma. Recently, survival rate is on the rise due to improved combination chemotherapy, radiotherapy and high dose chemotherapy followed by hematopoietic stem cell transplantation. In South Korea, no epidemiologic studies concerning malignant lymphoma in the pediatric age group has been performed. Therefore, the Korean Society of Pediatric Hematology-Oncology retrospectively analyzed the incidence, pathologic subtypes, treatment strategies, and survival rates of pediatric malignant lymphomas in South Korea. METHOD: Questionnaires were made and sent to a group of training hospitals, with a return of 580 questionnaires from 24 hospitals. Among them, 517 reports were suitable for analysis. RESULTS: Among the 517 cases, Hodgkin's disease accounted for 58 cases and non-Hodgkin's lymphoma for 459 cases. Male to female ratio for malignant lymphoma was 2.7. Mean age at diagnosis was 8.3 years. Among the pathologic subtypes, mixed cellularity was the most frequent subtype for Hodgkin's disease. Most (70.7%) cases of non-Hodgkins lymphoma belonged to high grade NHL. Burkitt lymphoma accounted for 102 cases, and lymphoblastic lymphoma was found in 58 cases. Peripheral lymphadenopathy was the most common presenting sign upon diagnosis. B symptoms were significantly more frequent in Hodgkin's disease patients than in non-Hodgkin lymphoma patients. The Complete response rate was 62.1% for non-Hodgkin's lymphoma, and 82.8% for Hodgkin's disease. Overall 5 year survival rate was 60.0% in non-hodgkin's lymphoma, and 84.8% in Hodgkin's disease. CONCLUSION: The annual incidence of malignant lymphoma in Korea is 4.7 per million. In cases of chemotherapy-sensitive, refractory or relapsed malinant lymphoma, high dose chemotherapy followed by hematopoietic stem cell transplantation is vital for improved survival. For more systematic analysis of epidemiology on malignant lymphomas, better surveillance mechanisms on the occurrence of malignant lymphomas are crucial, and establishment of standardized treatment protocol for malignant lymphoma is required.
Burkitt Lymphoma ; Child* ; Clinical Protocols ; Diagnosis ; Drug Therapy ; Drug Therapy, Combination ; Epidemiologic Studies ; Epidemiology* ; Female ; Hematopoietic Stem Cell Transplantation ; Hodgkin Disease ; Humans ; Incidence ; Korea* ; Lymphatic Diseases ; Lymphoma* ; Lymphoma, Non-Hodgkin ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Surveys and Questionnaires ; Radiotherapy ; Retrospective Studies* ; Survival Rate

PURPOSE: The annual incidence of aplastic anemia (AA) in Asian countries is higher than in Western countries. The pathogenesis in AA has been investigated in hematopoiesis and immunology. Recently, the survival rate and the quality of life of the patients with AA have been steadily improved by the development of a variety of treatments such as the immunosuppressive therapy (IST), and hematopoietic stem cell transplantation (HSCT). The Korean Society of Pediatric Hematology-oncology retrospectively investigated the incidence, treatment strategies, survival rate, and time to become independent from transfusion in patients with AA, who were diagnosed from January 1st, 1991 to December 31st, 2000 in Korea. METHODS: All the questionnaires were sent to a group of training hospitals, and we collected about 600 questionnaire forms from 27 hospitals. However, 493 reports were available for data analysis. RESULTS: The male and female ratio in AA is 1.1 (259 males vs. 234 female). The median age at diagnosis is 9 years old (range; 0.8~16 years old). The annual incidence of children with AA in Korea is 4.5 per million on the basis of Korean pediatric population. In etiology, there are 20 cases (4.1%) in congenital and others in acquired AA. In acquired AA, the cause of illness was not identifiable for most of the patients, but 1 patient had hepatitis-associated AA, and 3 patients developed the illness after medication. According to the initial laboratory data at diagnosis, the peripheral blood findings showed that hemoglobin is 7.1+/-2.4 g/dL, white blood cell 3, 200/microL (200~16, 550), absolute neutrophil counts 670/microL (0~12, 487), platelets 19, 000/microL (1, 000~500, 000), and corrected reticulocytes 0.18% (0.0~4.7). The bone marrow examination revealed that cellularity was below 25% in 348 patients, and over 25% in 105 patients. In the available data, 269 patients (54.6%) were diagnosed of severe aplastic anemia (SAA) and 224 patients of non-SAA (NSAA). HSCT were done for 96 patients (19.5%) and others received another treatments such as the IST. The anti-thymocyte globulin (ATG) or anti-lymphocyte globulin (ALG) treatment was done for 263 cases, corticosteroids for 259, cyclosporine A (CSA) for 215, and anabolic steroids for 138. The combination IST including ATG or ALG plus corticosteroid plus CSA were applied to 154 children with AA, and transfusion only in 37, as conservative care. In case of those patients with HSCT, the time from diagnosis to transplantation was 12 months (1~144 months) and the sources of stem cells were bone marrow in 82 cases, growth factor mobilized peripheral blood in five, and cord blood in six. There were 57 patients transfused below 40 units of blood products before HSC transplantation. Graft rejection was identified from 16 patients, and booster transplantations were done for 12 patients among them. In complications of HSCT, the graft versus host disease was developed in 20 patients and viral diseases in 12 cases including the CMV, herpetic infection, and hepatitis. Also, one patient suffered from veno-occlusive disease. The overall survival rate in children with AA is 64.3%. The survival rate in HSCT is better than that IST (76.9% vs. 62.6%, P< 0.05). In IST, overall survival rate in very SAA showed lower than SAA and NSAA, and in SAA lower than NSAA in case of absolute neutrophil count below 200/microL (P< 0.05). There was no significant difference in terms of the sex, age at beginning of treatment. In HSCT, transfusion was not related to the survival rate. However, overall survival rate is better in short interval between diagnosis and HSCT than in long interval (P< 0.05). There was no significant difference in the probability of transfusion independence according to treatment strategies, even though it was 71.0% in HSCT and 12.8% in immunosuppressive therapy at the end point of survey (P=0.47). The response pattern was as follows. There were 155 cases of complete response, 110 of partial response and 120 of no response in spite of various treatments. The relapse after treatment was found in 11 patients after IST, of which 6 patients experienced more than 2nd relapse. The median time between the end of treatment and relapse was 16 months (6~84 months). Only three cases developed into other diseases (1 case into acute myeloid leukemia and 2 cases into myelodysplastic syndrome). The median time from diagnosis to the end of treatment was 62 months (0.5~174 months). In fatal cases, the median time between diagnosis and death was 29 months (0~144 months) despite several therapeutic strategies. CONCLUSION: In Korea, the annual incidence of children with AA is 4.5 per million. This result is similar to the ones reported in other Asian countries, but higher than those in Western countries. Although a lot of children with AA received various therapies including IST or HSCT, new treatment strategies have to be developed to improve the survival rate and the quality of life of children with AA
Adrenal Cortex Hormones ; Allergy and Immunology ; Anemia, Aplastic* ; Antilymphocyte Serum ; Asian Continental Ancestry Group ; Bone Marrow ; Bone Marrow Examination ; Child* ; Cyclosporine ; Diagnosis ; Epidemiology* ; Female ; Fetal Blood ; Graft Rejection ; Graft vs Host Disease ; Hematopoiesis ; Hematopoietic Stem Cell Transplantation ; Hepatitis ; Humans ; Incidence ; Korea* ; Leukemia, Myeloid, Acute ; Leukocytes ; Male ; Neutrophils ; Quality of Life ; Surveys and Questionnaires ; Recurrence ; Reticulocytes ; Retrospective Studies* ; Statistics as Topic ; Stem Cells ; Steroids ; Survival Rate ; Virus Diseases

PURPOSE: Neutropenia is common in patients receiving myelotoxic chemotherapy. The aim of this study is to compare the efficacy, safety and adverse events between prophylactically administered Leukokine and Grasin. METHODS: An open-label, randomized, phase III study was designed to compare the effects of a subcutaneous injection of Leukokine (CJ Corp.) 100mug/m2 with Grasin (Jeil Pharm. Inc.) in patients receiving induction chemotherapy for acute leukemia. All patients received one dose of G-CSF every day during the study period. Total period of G-CSF injection was not over 14 days. The administration of G-CSF began on day 14 after beginning of chemotherapy under CCG strategy. In other chemotherapies, the injection of G-CSF started on day 1 from end of chemotherapy. Injection of G-CSF stopped after absolute neutrophil count recovery was achieved. RESULTS: The median numbers of times of administration were 9.6 (2~14) /cycle for Leukokine and 8.8 (2~14) /cycle for Grasin. The time to needed for neutrophil recovery more than 1, 000/mm3 was 6.6 4.9 day and 4.7 4.8 day of the Leukokine and Grasin, respectively (P=0.14). The mean duration of neutropenia less than 500/mm3 was 7.6 5.6 days for Leukokine and 6.1 6.0 days for Grasin (P=0.28). The results for the two groups were also not significantly different in adverse events, physical examination and laboratory findings. CONCLUSION: Leukokine was safe and well tolerated in these patients population. Injection of Leukokine provided neutrophil recovery with safety and efficacy similar to that provided by Grasin.
Drug Therapy ; Granulocyte Colony-Stimulating Factor ; Humans ; Induction Chemotherapy* ; Injections, Subcutaneous ; Leukemia* ; Neutropenia ; Neutrophils ; Physical Examination

PURPOSE: Childhood acute immune thrombocytopenic purpura (ITP) is a benign hematologic disease. Therapy does not affect the natural history of the illness. We evaluated the clinical and laboratory findings, treatment and prognosis of childhood acute ITP in Korea through a retrospective multicenter study. METHODS: We analyzed retrospectively the data of 1, 829 children with acute ITP through survey of 33 hospitals among 43 hospitals in Korea from Sep. 1992 to Aug. 2001. RESULTS: Male to female ratio was 1.3: 1 and the median age at the diagnosis of ITP was 2.9 (0.1 17) years. Median duration of follow up was 6 months. One hundred and forty nine cases of the total 1, 829 patients (8.1%) received no treatment. The initial median platelet count of the non-treated group was 42, 500/mm3. Among the 861 cases who were followed up over 6 months, 315 cases (36.6%) progressed into chronic ITP. Associated with this high rate of chronicity of childhood acute ITP patients in Korea, we must consider the fact that acute ITP patients with fast improvement in the first episode tend not to follow up. Considering that fact, the rate of chronicity becomes 17.2% of the 1, 829 acute ITP patients. The treated group used many kinds of treatment methods. Intravenous immunoglobulins (IVIG) with or without prednisolone (PD) (67.5%) were the most commonly used regimens. In the group treated with IVIG alone, the platelet count began to rise above 50, 000/mm3 at 2.6 days, 100, 000/mm3 at 3.7 days and 150, 000/mm3 at 4.9 days. Four hundred and twenty two cases of the 1, 686 (25.0%) cases followed up after first episode of ITP relapsed. The relapse rate was significantly higher in older patients and in girls than in younger patients and in boys (P< 0.05). The chronicity of ITP statistically increased with age (P< 0.05) and that was the only valuable factor. CONCLUSION: Despite the fact that childhood acute ITP is a pretty common disaese, there is no agreement on the best treatment method for this disease. The establishment of Korean treatment guideline of childhood acute ITP, based on an analysis of multicenters, seems to be needed.
Child ; Diagnosis ; Female ; Follow-Up Studies ; Hematologic Diseases ; Humans ; Immunoglobulins, Intravenous ; Korea* ; Male ; Natural History ; Platelet Count ; Prednisolone ; Prognosis ; Purpura, Thrombocytopenic, Idiopathic* ; Recurrence ; Retrospective Studies